Topical drug delivery• Skin anatomy

• Functions of skin

• Five main target regions in dermatological therapy

• Sunscreen on skin surface

• Acne to target hair follicles and pilosebaceous unites

• Delivery of macromolecules via the hair follicles

• Contact dermatitis and viable epidermis and dermis

Skin anatomy• Epidermis --0.8 to 0.006 mm. --stratum corneum: 10 m when dry, horny

layer (10-20% moisture)

• Dermis --3-5 mm --a matrix of connective tissues woven fibrous

proteins --Nerves, blood vessels (< 0.2 mm deep),

lymphatics

• Subcutaneous tissue --mechanical cushion, thermal barrier, energy

storage

• Appendages --Sweat glands --hair follicles --Sebaceous glands --Nails

Functions of skin

• Mechanical function -- mainly from the dermis and s.c. tissues -- epidermis (minor) • Protective function -- Microbiological barrier -- Chemical barrier -- Radiation barrier -- Heat barrier/temperature regulation -- Immune response

Stages on percutaneous absorption from a suspension ointment

Five main target regions in dermatology

• Surface treatment -- Camouflage, protective layer, insect repellent,

antimicrobial/antifungal, Sunscreen• Stratum corneum -- Emollient, keratosis• Skin appendage -- Acne, antibiotics, depilatory, antiperspirant, vaccine• Viable epidermis/dermis -- antiinflammation, anesthetics, antihistamine,

antipruritic• Systemic treatment -- transdermal

Sunlight, sunscreen, suntan

UVA: suntan, and PUVA treatment of psoriasis (psoralen + UVA),

photosensitivity, photoaging, photodermatoses, and augment cancerous effects of UVB.

UVB: Vitamin D synthesis

Cause sunburn, skin cancers

UVC

UV spectrum

Factors affecting exposure to UVR

Time of the day, Altitude, environmental factors, and predisposed factors.

Suntan and sunburn• Sun tanning: a result of two processes -- Oxidation of melanin/immediate darkening -- Stimulation of melanocytes/delayed tanning Tanning increases tolerance to additional sun light.

• Sunburn: a superficial burn involving the epidermis.

-- Normal sequence -- Erythema, 20-30 min, oxidation of melanin and dilation of dermal

venules -- True sunburn erythema, 2-8 h -- Localized edema and pain, 14-20 h, last 1-3 days

• Other reactions to UVR -- actinic keratosis, squamous cell carcinoma, basal cell carcinoma,

melanoma.

Sunscreen agents• SPF: Minimal, 2-12; Moderate, 12-30

high, > 30

SPF is the minimal erythema dose (MED) of protected skin over the MED of unprotected skin. MED is the amount of solar radiation needed to produce minimal skin redness.

• Types of sunscreens Physical sun blockers Titanium dioxide, Zinc oxide, Red

petrolatum

Chemical sun absorbers (1) PABA (2) Cinnamates (3) Salicylates (4) Benzophenones (5) Avobenzone (Parsol 1789)

Physical blockers are opaque formulations that reflect and scatter up to 99% of light in both VR and vis ranges.

Less cosmetically acceptable/greasy.

Sunscreens just need to bind and remain on the skin for sufficient time.

Dihydroxyacetone (DHA)

ErythruloseCoppertone

DHA is a chemical agent that darkens the skin by reacting with keratin in the stratum corneum to produce artificial suntan. It provides no protection against UV rays, and may not be natural looking. The Eryhtrulose is also in some products. It can be in lotion, gel, spray, solution, etc.

Acne• Acne vulgaris is a disorder of the pilosebaceous units.• A plug of the pilosebaceous duct and follicle opening. • Drugs have to get into the hair follicles and pilosabaceous units

http://www.skincarephysicians.com/acnenet/acne.html

Etiology• Increased sebum production Androgens regulate sebum production. Testosterone converted to DHT,

which induces sebaceous glands to increase in size and activity, resulting in

increased amount of sebum. • Abnormal clumping of epithelial horny cells in

the pilosebaceous unit Horny cells usually sloughed off from epithelial lining of the pilosebaceous

duct. Retention hyperkeratosis (increased adherence and production of follicular

epithelial cells)

• Presence of Propionibacterium acnes P. acnes lipases break triglyceride to fatty acids, which are irritating, cause

comedones, and result in inflammation.

Assessment of acne severity

Grade Qualitative description Quantitative description

I Comedonal acne Comedones only, < 10 on face, none on trunk, no scars, non-inflammatory lesion

II Papular 10-25 papules, mild scarring, inflammatory lessoin (< 5 mm)

III Pustule 25 pustules, moderate scarring

IV Pustulocytic acne Nodules or cysts, extensive scarring, inflammatory lessions . 5 mm.

Cytic acne Extensive nodule/cysts

Self treatment with OTC agents is only OK for grade I.

Approaches for treatment

• Increased sebum production

Testosterone converted to DHT, which induces sebaceous glands size and activity.

• Abnormal clumping of epithelial horny cells in the pilosebaceous unitRetenion hyperkeratosis

• Presence of Propionibacterium acnes

P. acnes lipases break triglyceride to fatty acids, which are irritating, causing comedones.

Decreasing the amount of sebum produced

Unblocking the sebaceous ducts

Kill the bacteria

OTC acne product• Benzoyl peroxide -- 2.5% to 10% -- Most effective OTC -- Kill P. acnes and irritant to increase epithelial cell

turnover rate. -- gel, cream, or lotion• Salicylic acid -- 0.5-2%, irritant keratolytic agent, lotion, creams• Sulfur, 3-8% combined with resorcinol 2%, or resorcinol

monacetate 3%. keratolytic and antibacteria, color/odor• Resorcinol -- 1-4%, keratolytic when combined with sulfur

Prescription• Tretinoin (retin-A): • increase the turnover rate of

nonadhering horny cells in follicles.• Cream, gel, topical solution• More effective agent for acne• Increase hair growth

• Others: Adapalene (Differin), Tazarotene gel and cream (Tazorac), antibiotics (tetracyline, erythromycin, clindamycin, etc)

• Isotretinoin (Accutane)• For severe racalcitrant nodulocytic

acnes• Decrease sebum and keratinization• Reduce population of P. acnes• Birth defect

Tretinoin is very effective

Hair follicular cycle

Human: Normally up to 90% of the hair follicles are in anagen phase while, 10–14% are in telogen and 1–2% in catagen.

Rodent: hair follicles are synchronized in the first two cycles.

Hair follicles as a route for drug/vaccine delivery

Macromolecules access skin via hair follicles

Contact dermatitis:Inflammation of the skin

Irritant contact dermatitis

Caused by direct contact with the irritant Absolute primary irritants: acids, alkalis, industrial chemicals, Relative primary irritants: soaps, detergent, benzoyl peroxide, etc)

Allergic contact dermatitis: The result of direct contact with a contact allergen, such as poison

ivy and nickel. Allergic contact dermatitis is considered a T-cell mediated delayed-response immune reaction, because elicitation of an allergic reaction typically takes 48 to 72 hours to occur after reexposure to the same allergen.

Allergic contact dermatitis1. Hapten contacts skin

epidermis

2. Hapten complexes with protein

3. Hapten-protein enters lymphatic systems

4. Generation of specific Th1 CD4+ and CD8+ T cells.

5. Re-exposure

6. Dermatitis responses

Urushiol from poison ivy, poison oak, and sumac.

Hapten = small molecules that are only antigenic when combined with a carrier protein.

http://www.poison-ivy.org/

Treatments

• Severe eruptions: systemic corticosteriods

• Less severe eruptions:

Relieve itching Local anesthetics (benzocaine)

Antihistamines (oral or topical, mainly sedative effect)

Topical hydrocortisone

Treatment Topical hydrocortisone.

Topical corticosteriod preparations

Some brand names of hydrocortisone